Gene patterns guide prognosis in castration-resistant prostate cancer

In two recent studies, one research team identified genes that can predict outcomes in men with castration-resistant prostate cancer (CRPC) while another group of investigators found a different set of genes with similar predictive properties.

In one project, reported in The Lancet Oncology, Johann S. de Bono, MD, of the Institute of Cancer Research in London, United Kingdom, and colleagues analyzed messenger RNA (mRNA) expression arrays in blood samples taken from 100 men with prostate cancer to identify patients with metastatic CRPC with poorer outcomes. Most of the men (69) had CRPC, and 31 control patients were thought to have low-risk, early-stage prostate cancer.

The 94 evaluable patients were divided into four groups based on patterns of gene activity reflected in the blood samples. Upon reviewing the men's progress over nearly 2.5 years, the investigators found that in one group, the men with CRPC had survived for significantly less time than did men in the other groups.

Further statistical modeling identified nine key active genes that were shared by all the patients in that group. Testing in another 70 men with advanced cancer showed that these nine genes alone could be used to accurately identify patients who ultimately survived for a shorter time: 9.2 months for those with this particular gene pattern, compared with 21.6 months for men without this gene pattern. The fact that a number of these nine genes were involved in the immune system suggests immunosuppression in men whose cancers metastasized.

The other study, which also appeared in The Lancet Oncology, was conducted by William K. Oh, MD, of the Division of Hematology/Oncology at the Tisch Cancer Institute of Mount Sinai, New York, New York, and colleagues. They sought to assess the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in CRPC.

Oh's team found that a six-gene model separated men with CRPC into two risk groups:

a low-risk group with a median survival of more than 34.9 months (median survival was not reached), and

a high-risk group with a median survival of 7.8 months.

The prognostic utility of the six-gene model was validated in an independent cohort. Similar to the nine-gene model identified by de Bono's group, the six-gene model suggests possible dysregulation of the immune system.